A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets.

Abstract:

:Pandemic outbreaks of influenza are caused by the emergence of a pathogenic and transmissible virus to which the human population is immunologically naïve. Recent outbreaks of highly pathogenic avian influenza (HPAI) of the H5N1 subtype are of particular concern because of the high mortality rate (60% case fatality rate) and novel subtype. In order to develop a vaccine that elicits broadly reactive antibody responses against emerging H5N1 isolates, we utilized a novel antigen design technique termed computationally optimized broadly reactive antigen (COBRA). The COBRA HA sequence was based upon HA amino acid sequences from clade 2 H5N1 human infections and the expressed protein retained the ability to bind the receptor, as well as mediate particle fusion. Non-infectious recombinant VLP vaccines using the COBRA HA were purified from a mammalian expression system. Mice and ferrets vaccinated with COBRA HA H5N1 VLPs had protective levels of HAI antibodies to a representative isolates from each subclade of clade 2. Furthermore, VLP vaccinated animals were completely protected from a lethal challenge of the clade 2.2 H5N1 virus A/Whooper Swan/Mongolia/244/2005. This is the first report describing the use of COBRA-based antigen design. The COBRA HA H5N1 VLP vaccine elicited broadly reactive antibodies and is an effective influenza vaccine against HPAI virus.

journal_name

Vaccine

journal_title

Vaccine

authors

Giles BM,Ross TM

doi

10.1016/j.vaccine.2011.01.100

subject

Has Abstract

pub_date

2011-04-05 00:00:00

pages

3043-54

issue

16

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(11)00172-1

journal_volume

29

pub_type

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